Metabolic and endocrine connections of 17-hydroxypregnenolone in polycystic ovary syndrome women

Abstract

ObjectiveTo examine the anthropometric, and metabolic connections of 17-hydroxypregnenolone in the normo- and hyperandrogenemic polycystic ovary syndrome phenotypes.Materials and methodsThis cohort study was conducted at the Julio Muller University Hospital, Cuiabá, Brazil, between January 2014 and July 2016, and 91 normal cycling healthy women, 46 normoandrogenemic and 147 hyperandrogenemic, patients with polycystic ovary syndrome (PCOS) were enrolled according to the Rotterdam criteria. Several anthropometric, biochemical and hormonal parameters were properly verified and correlated with 17-hydroxypregnenolone (17-OHPE) concentrations.Results17-OHPE was higher in hyperandrogenemic PCOS than in normoandrogenemic PCOS and in control groups (P = 0.032 and P < 0.001, respectively). In healthy controls, 17-OHPE was positively associated with glucose, free estrogen index, DHEAS and negatively associated with compounds S. In normoandrogenemic PCOS patients, 17-OHPE presented positive correlations with VAI, LAP, cortisol, insulin and HOMA-IR. In the hyperandrogenemic group, 17-OHPE presented significant negative correlations with most anthropometric parameters, HOMA-IR, HOMA %B, estradiol, free estrogen index (FEI), C-peptide, and TG levels and positive correlations with HOMA-S and high-density lipoprotein cholesterol (HDL-C), sex-hormone binding globulin (SHBG), androstenedione (A4) and dehydroepiandrosterone (DHEA). Regarding hyperandrogenemic PCOS, and using a stepwise multiple regression, only HOMA-S and WHR were retained in the model (R2 = 0.294, P < 0.001).Conclusion17-OHPE exhibited different relationships with anthropometric, and biochemical parameters in PCOS patients, depending on the androgen levels. In PCOS subjects with high androgen concentrations, 17-OHPE was negatively associated with most anthropometric parameters, particularly with those used as markers of adipose tissue dysfunction and frequently employed as predictors of cardiovascular disease risk; otherwise, 17-OHPE was positively associated with HDL-C and HOMA-S in this patients. Future studies are required to evaluate the clinical implications of these novel findings.

Changes in clinical and biochemical characteristics of polycystic ovary syndrome with advancing age

“…In addition, this parameter should not be used to define PCOM in adolescent PCOS (11,25). Classic 21-hydroxylase, 3β-hydroxysteroide dehydrogenase II (3β-HSDII) and 11β-hydroxylase deficiencies were excluded in the cases of 17-hydroxyprogesterone (17-OHP4) levels ≤5 ng/mL (≤15 nmol/L), 17-hydroxypregnenolone (17-OHPE) <0.42 ng/mL (<13.5 nmol/L), and compound S <0.8 ng/mL (<23 nmol/L) (26,27). Primary hypothyroidism was excluded by a thyroid-stimulating hormone (TSH) level of ≤4.2 µUI/mL and free thyroxin (fT4) level of ≤9.0 pmol/L (28,29).…”

“…Frequent menses were defined as more than four menstrual episodes in a 90-day period, and infrequent menses were defined as menstrual cycle ≥45 days or ≤8 menstrual period in the past year (14,32,33). Biochemical hyperandrogenism was defined by at least one of the following criteria: total testosterone ≥2.1 nmol/L, free testosterone (FT) ≥0.03 pmol/L, dehydroepiandrosterone sulfate (DHEAS) ≥6.7 µmol/L, androstenedione (A4) ≥8.6 nmol/L, and free androgen index (FAI) ≥6 (27). Impaired fasting glucose (IFG) was defined by fasting plasma glucose concentration >100 mg/dL (5.5 mmol/L) or <126 mg/dL (7.0 mmol/L).…”

“…Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured with the study participants in a sitting position after at least 5 min of resting. Because inconsistent results due to ethnicity and inter-rater evaluation, the Ferriman-Gallwey score was not used and the clinical hyperandrogenism was registered as dichotomous variable, according to the patient's complaints and the presence or the lack of hirsutism in the upper lip, chin, chest, upper or lower back, upper or lower abdomen, upper arms and thighs (27,36). Ovarian morphology was examined by ultrasonography, using a vaginal transducer with a frequency of 5-8 MHz (Toshiba Xario SSA-660A, Toshiba Medical do Brazil LTDA, Taboão da Serra, SP, Brazil or Voluson ® E8, GE Health Care, United Kingdom).…”

Relationship of Biological Markers of Body Fat Distribution and Corticosteroidogenic Enzyme Activities in Women with Polycystic Ovary Syndrome

“…NA-PCOS, HA-PCOS and normal cycling women were compared to assess whether they present differences in the corticosteroidogenic enzyme activities among them. According to several robust publications, biochemical hyperandrogenemic PCOS may be defined by the presence of one or more of the following biochemical parameters: T ≥ 2.1 nmol/l, free T ≥ 0.027 pmol/l, DHEA ≥ 6.7 μmol/l, A4 ≥ 8.6 nmol/l, and free androgen index (FAI) ≥ 6 [22][23][24][25]. Patients who had used sex steroids or insulin sensitizing drugs over the last six months or who did not fulfill the Rotterdam criteria were excluded.…”

“…Oral glucose tolerance test (OGTT) was performed by measuring glucose before and 120 min after 75 g oral dextrose. All hormone measurements were detailed in a recent publication [33]. The level of 17-OHPE was measured with an HPLC/MS/MS (Labco Nous Advanced Special Diagnostics, SP, Brazil).…”